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Efficacy and Low Toxicity of Normo-Fractionated Re-Irradiation with Combined Chemotherapy for Recurrent Glioblastoma—An Analysis of Treatment Response and Failure
No full textBackground: Glioblastoma is the most common malignant brain tumor in adults. Even after maximal safe resection and adjuvant chemoradiotherapy, patients normally relapse after a few years or even months. Standard treatment for recurrent glioblastoma is not yet defined, with re-resection, re-irradiation, and systemic therapy playing key roles. Usually, re-irradiation is combined with concurrent chemotherapy, harnessing the radiosensitizing effects of alkylating agents. Methods: A retrospective analysis of 101 patients with recurrent glioblastoma treated with re-irradiation was conducted, evaluating the survival impact of concurrent chemotherapy regimens, as well as prior resection. Patients were subcategorized according to concurrent chemotherapy (temozolomide vs. CCNU vs. combination of both vs. none) and details are given regarding treatment toxicity and patterns of relapse after first- and second-line treatment. Results: Patients were treated with normo-fractionated re-irradiation (with prescription dose of ~40 Gy to the PTV), resulting in a moderate cumulative EQD2 (~100 Gy). The mean overall survival was 11.3 months (33.5 months from initial diagnosis) and mean progression free survival was 9.5 months. Prior resection resulted in increased survival (p < 0.001), especially when gross total resection was achieved. Patients who received concurrent chemotherapy had significantly longer survival vs. no chemotherapy (p < 0.01), with the combination of CCNU and TMZ achieving the best results. Overall survival was significantly better in patients who received the CCNU + TMZ combination at any time during treatment (first or second line) vs. monotherapy only. The treatment of larger volumes (mean PTV size = 112.7 cm3) was safe and did not result in worse prognosis or increased demand for corticosteroids. Overall, the incidence of high-grade toxicity or sequential radionecrosis (5%) was reasonably low and treatment was tolerated well. While second-line chemotherapy did not seem to influence patterns of relapse, patients who received TMZ + CCNU as first-line treatment had a tendency towards better local control with more out-field recurrence. Conclusions: Normo-fractionated re-irradiation appears to be safe and is accompanied by good survival outcomes, even when applied to larger treatment volumes. Patients amenable to undergo re-resection and achieving concurrent systemic therapy with alkylating agents had better OS, especially when gross total resection was possible. Based on existing data and experiences reflected in this analysis, we advocate for a multimodal approach to recurrent glioblastoma with maximal safe re-resection and adjuvant second chemoradiation. The combination of TMZ and CCNU for patients with methylated MGMT promoter yielded the best results in the primary and recurrent situation (together with re-RT). Normo-fractionated RT enables the use of more generous margins and is tolerated well
Globalisierung und Digitalisierung:Internationalisierung von Unternehmen und Nutzung digitaler Ressourcen
No full textThis research paper explores the relationship between firm internationalisation and digital resource use. On the one hand, the modularity of digital resources and their applicability in different international contexts provide significant benefits to multinational companies. On the other hand, the complexity of managing digital resources across different institutional systems escalates with rising levels of internationalisation. Because of these competing forces, I argue that the relationship is inversely U-shaped. Additionally, I investigate the moderating effect of firms' financial constraints and conjecture a steepening effect of the inverted U-shape. In my empirical identification strategy, I employ a text-based measure of internationalisation, based on companies' 10-K annual reports, and combine this measure with data on internet and e-commerce technology used by Standard & Poor's 1,500 firms. The results provide empirical support of an inverse U-shaped relationship and the moderating role of financial constraints. Various robustness tests corroborate the findings. This study contributes to the literature streams of firm internationalisation and information systems research by highlighting the trade-offs faced by MNEs when they "go digital".Diese Studie untersucht den Zusammenhang zwischen der Internationalisierung von Unternehmen und der Nutzung digitaler Ressourcen. Einerseits bieten die Modularität digitaler Ressourcen und ihre Anwendbarkeit in verschiedenen internationalen Kontexten erhebliche Vorteile für internationale Unternehmen. Andererseits nimmt die Komplexität der Verwaltung digitaler Ressourcen über verschiedene institutionelle Systeme hinweg mit zunehmenden Internationalisierungsgrad zu. Aufgrund dieser konkurrierenden Kräfte argumentiere ich, dass sich die Beziehung durch ein umgekehrtes U beschreiben lässt. Darüber hinaus untersuche ich die moderierende Wirkung von finanziellen Beschränkungen und vermute eine Streckung des Zusammenhangs. In der empirischen Identifikationsstrategie verwende ich ein textbasiertes Maß zur Messung der Internationalisierung von Unternehmen, das auf 10-K-Jahresberichten US-amerikanischer Unternehmen des S&P 1.500 Index basiert, und kombiniere dieses mit Daten zu Internet- und E-Commerce-Technologien sowie Buchhaltungs- und Finanzkennzahlen. Die Ergebnisse unterstützen die Hypothesen einer umgekehrt U-förmigen Beziehung sowie der Moderation durch finanzielle Beschränkungen. Mehrere Robustheitstests untermauern die Ergebnisse. Diese Studie leistet einen Beitrag zur Literatur im Bereich der Unternehmensinternationalisierung und Informationssysteme, indem sie Zielkonflikte aufzeigt, denen sich multinationale Unternehmen gegenübersehen, wenn sie digitalisieren
Visual perceptual load and processing of somatosensory stimuli in primary and secondary somatosensory cortices
No full text'Load theory' assumes that neural activation to distractors in early sensory cortices is modulated by the perceptual load of a main task, regardless of whether task and distractor share the same sensory modality or not. While several studies have investigated the question of load effects on distractor processing in early sensory areas, there is no functional magnetic resonance imaging (fMRI) study regarding load effects on somatosensory stimuli. Here, we used fMRI to investigate effects of visual perceptual load on neural responses to somatosensory stimuli applied to the wrist in a study with 44 participants. Perceptual load was manipulated by an established sustained visual detection task, which avoided simultaneous target and distractor presentations. Load was operationalized by detection difficulty of subtle or clear color changes of one of 12 rotating dots. While all somatosensory stimuli led to activation in somatosensory areas SI and SII, we found no statistically significant difference in brain activation to these stimuli under high compared to low sustained visual load. Moreover, exploratory Bayesian analyses supported the absence of differences. Thus, our findings suggest a resistance of somatosensory processing to at least some forms of visual perceptual load, possibly due to behavioural relevance of discrete somatosensory stimuli and separable attentional resources for the somatosensory and visual modality
A determinant formula for Toeplitz operators associated to a minimal flow
No full textWe define a determinant on the Toeplitz algebra associated to a minimal flow, give a formula for this determinant in terms of symbols, and show that this determinant can be used to give information about the algebraic K-theory of functions on the underlying space
Conformations of the three gates in Saccharomyces cerevisiae topoisomerase II and their response to DNA, nucleotide, and etoposide
No full textEukaryotic topoisomerase II (TOP2) catalyzes DNA relaxation and decatenation in an ATP-dependent reaction. TOP2 is a homodimer with three protein–protein interfaces, the N-gate, DNA-gate, and C-gate. Relaxation and decatenation follow a strand-passage mechanism in which one DNA duplex is bound at the DNA-gate in the middle of the enzyme and cleaved, a second DNA duplex is captured by ATP-induced closing of the N-gate through dimerization of the ATPase domains, the DNA-gate opens to enable passage of the second duplex through the gap, then closes for religation of the cleaved duplex, and the C-gate opens to release the second duplex. ATP hydrolysis and re-opening of the N-gate complete the catalytic cycle. Despite their key role in the topoisomerase reaction, gate opening and closing have not been observed directly. Here we use single-molecule FRET and 'Saccharomyces cerevisiae' TOP2 labeled with donor and acceptor fluorophores on opposite sides of the N-gate, the DNA-gate, or the C-gate to investigate the conformational changes of these gates in response to nucleotide, DNA, and the topoisomerase poison etoposide. We show that the N-gate is open in the absence of nucleotides, and closes in response to nucleotide binding. The DNA- and C-gates are in a closed state in the absence of nucleotide and DNA and in the nucleotide-bound state. In the presence of DNA, DNA and nucleotide, or etoposide, conformations with widened or open DNA- or C-gates are observed. Consistent with biochemical data, our results point to a tight coupling between the events at different gates and between the conformational changes of these gates
Der Zusammenhang zwischen bewusster Emotionsverarbeitung und Coping-Stilen (Rumination, Distraktion) bei Major Depressive Disorder
No full textRumination und gestörte Emotionsverarbeitung gelten als zentrale Merkmale der Major Depressive Disorder (MDD). Rumination lässt sich in symptom- (SYM) und selbstfokussiert (SELF) unterteilen und steht im Kontrast zur Distraktion (DIS). Ziel dieser Arbeit war es, Zusammenhänge zwischen diesen Coping-Stilen und der Amygdala-Aktivierung bei MDD während des Hariri-Paradigmas zu untersuchen. 181 akut depressive Patienten füllten den RSQ-D aus und wurden mittels fMRT untersucht. Regressions- und Extremgruppenanalysen prüften, ob SYM und SELF mit einer verstärkten, DIS mit einer reduzierten Aktivierung assoziiert sind. Zwar zeigten sich erwartungskonforme Aktivierungen bei emotionalen Reizen, doch kein signifikanter Zusammenhang mit den Coping-Stilen. Die Hypothesen konnten nicht bestätigt werden
Development of a soft X-ray spectrometer for fluorescence photons emitted during laser cooling at SIS100 and of a fast high voltage divider for CRYRING@ESR
No full textDiese Arbeit behandelt Experimente mit hochgeladenen relativistischen Ionen am GSI Helmholtzzentrum und an der FAIR-Anlage mit dem SIS100. Im ersten Teil wird das Laser-Cooling-Projekt vorgestellt, in dessen Rahmen ein Spektrometer für Fluoreszenzstrahlung im weichen Röntgenbereich entwickelt wurde. Mithilfe dieses Systems lässt sich die Ionengeschwindigkeit über die Wellenlänge der Photonen rekonstruieren und der Kühlprozess überwachen. Zusätzlich wird eine Laserkühl-Teststrahlzeit am ESR mit 12C3+-Ionen beschrieben, bei der der Einsatz gepulster Laser zum Laserkühlen demonstriert wurde. Im zweiten Teil wird die Arbeit an dem schnellen Hochspannungsteiler FC20 beschrieben, der zur exakten Bestimmung der Elektronenenergie im CRYRING dient. Diese Energie ist entscheidend für die Kühlung und für Experimente zur dielektrischen Rekombination. Bei Spannungsmessungen während einer Strahlzeit mit Ne3+-Ionen konnte eine Genauigkeit von unter 5,8 ppm innerhalb von 10 ms erreicht werden.This thesis focuses on experiments involving highly charged relativistic ions conducted at the GSI Helmholtz Centre and the FAIR facility with the SIS100. The first part presents the laser cooling project, for which a fluorescence photon spectrometer operating in the soft X-ray range was developed. This system can be used to reconstruct the ion velocity via the wavelength of the photons and to monitor the cooling process. In addition, a laser cooling test beam time at the ESR with 12C3+ ions is described, during which the use of pulsed lasers for laser cooling was demonstrated. The second part describes the work on the fast high-voltage divider FC20, which is used to precisely determine the electron energy in the CRYRING. This energy is crucial for cooling and for experiments on dielectric recombination. Voltage measurements performed during a beam time with Ne3+ ions achieved an accuracy of less than 5.8 ppm within 10 ms
Die Dystopie in Zeiten der Klimakrise:Potenziale dystopischer Strukturen für eine (literarische) Bildung für nachhaltige Entwicklung
No full textDystopien sind ein aktuell stark rezipiertes und vermehrt beleuchtetes Phänomen gerade mit Blick auf den Klimawandel und den damit zusammenhängenden, oftmals dystopisch anmutenden öffentlichen Diskurs. Im Kontext der ebenfalls immer breiter diskutierten Frage, welche Rolle ein am Konzept der BNE orientierter Literaturunterricht in Zeiten des Klimawandels spielen kann und soll, wird häufig auf ihr Potenzial einer ‚Schockwirkung‘ und deren mögliche Auswirkungen verwiesen. Selten diskutiert wurde bis jetzt jedoch das mögliche Auftreten kognitiver Dissonanz im Leseprozess. Diese Arbeit soll Potenziale einer solchen kognitiven Dissonanz mit Blick auf die Rezeption von Dystopien näher beleuchten. Zudem soll die Frage nach Wirkstrukturen und Rezeption von Climate Change Fiction und spezifisch utopischen Texten mit Bezug auf Themen wie Verantwortung, Kinder- und Jugendliche als Weltretter, information versus perception gap, double think und ähnliche daran anschließende Konzepte gestellt werden
Dry side of the core: a meta-analysis addressing the original nature of the ABA signalosome at the onset of seed imbibition
No full textThe timing of seedling emergence is a major agricultural and ecological fitness trait, and seed germination is controlled by a complex molecular network including phytohormone signalling. One such phytohormone, abscisic acid (ABA), controls a large array of stress and developmental processes, and researchers have long known it plays a crucial role in repressing germination. Although the main molecular components of the ABA signalling pathway have now been identified, the molecular mechanisms through which ABA elicits specific responses in distinct organs is still enigmatic. To address the fundamental characteristics of ABA signalling during germination, we performed a meta-analysis focusing on the Arabidopsis dry seed proteome as a reflexion basis. We combined cutting-edge proteome studies, comparative functional analyses, and protein interaction information with genetic and physiological data to redefine the singular composition and operation of the ABA core signalosome from the onset of seed imbibition. In addition, we performed a literature survey to integrate peripheral regulators present in seeds that directly regulate core component function. Although this may only be the tip of the iceberg, this extended model of ABA signalling in seeds already depicts a highly flexible system able to integrate a multitude of information to fine-tune the progression of germination
Early Modern Dissertations in French Libraries: The EMDFL Dataset
No full textEMDFL contains aggregated metadata of up to 55 178 early modern dissertations in French libraries published between 1564 and 1800. It is the first attempt to capture metadata for early modern dissertations in a given region regardless of their country of origin. The data were retrieved from the union catalogue of French university libraries (SUDOC) and the general catalogue of the Bibliothèque Nationale de France (BNF), harmonized and reconciled. The process is documented in Python notebooks which are included in the dataset. The present paper includes reflections on challenges in using generalist categories for catalogization when dealing with early modern prints, because these categories are less refined and not always applied uniformly by cataloguers. Therefore, the overall data quality is lower than in the case of specialist bibliographies of early modern prints, e. g. the Verzeichnis deutscher Drucke. Nevertheless, the data facilitate fresh insights into the circulation of dissertation prints across Europe, allowing for data-guided analyses of knowledge exchange on a European scale